This proposal seeks to upgrade an existing 14 year old X-ray detector with a state-of-the-art HTC imaging plate detector and crystal cryo-cooling system. The instrument will be part of the macromolecular diffraction instrumentation facility at UCLA and will be dedicated to biochemical research supported by the NIH as well as other agencies. The instrumentation will also provide critical training for young scientists. The equipment requested is a state-of-the-art Rigaku HTC Image Plate detector and an X-STREAM 2000 crystal cryocooling system. The need for new instrumentation is driven by new developments in molecular crystallography, combined with the necessity of replacing outdated equipment in order to advance research on frontier problems. The new detector will make it possible to solve challenging molecular structures, particularly in cases where only small crystals can be obtained;this scenario is more and more common as scientists attack increasingly complex molecular structures, and as robotic methods produce crystals at an increasing speed, but often of decreasing size. The new equipment will support six major users and eight minor users working on NIH-supported research projects related to biomedical problems including but not limited to: neurodegenerative diseases, blood clotting, cellular signaling and cancer, heart disease, and microbial infection. New equipment is required to replace an old and outdated RAXIS4 detector which has served well for 14 years of nearly continuous use, but is nearing the end of its lifespan. Maintenance and replacement of worn parts on that detector is becoming problematic. Besides being new and requiring less frequent repair, the new equipment will be more sensitive and will have a faster readout, which will make it possible to obtain high quality diffraction data faster on a larger range of macromolecular crystals. With this important upgrade we will be able to prevent data collection from limiting progress on our scientific research problems. The macromolecular X-ray facility at UCLA is remarkable for the breadth and number of separate research groups it supports, and for the in-depth teaching it provides to large numbers of structural biologists-in- training. The new instrument will make it possible to continue and advance these important missions. HEALTH RELEVANCE: The proposed research advances our understanding of the structures of biological molecules and the roles they play in health and diseases. The fundamental biological insights to be gained will bear on biomedical issues including: neurodegenerative diseases, blood clotting, cellular signaling and cancer, heart disease, microbial infection, and others. To enable that research, this proposal requests X-ray diffraction equipment that will be utilized by at least 14 different research groups.